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出境医 / 临床实验 / Extra-Corporeal Carbon Dioxide Removal in Exacerbations of Chronic Obstructive Pulmonary Disease

Extra-Corporeal Carbon Dioxide Removal in Exacerbations of Chronic Obstructive Pulmonary Disease

Study Description
Brief Summary:
Around 20% of the patients requiring hospitalization for Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD) develop hypercapnia, which is associated with an increased risk of death. Once Non Invasive Ventilation (NIV) has been initiated, a reduction in Respiratory Rate (RR) and improvement in pH within 4 h predicts NIV success. If pH <7.25 and RR >35 breath per minutes persist, NIV failure is likely. Worsening acidosis, after initial improvement with NIV, is also associated with a worse prognosis. In addition, it has been shown that delaying intubation in patients at high risk for NIV failure has a negative impact on patient survival. Hence, assessing the risk of NIV failure is extremely important. NIV has some limitations: a) intolerance, discomfort and claustrophobia requiring frequent interruptions; b) poor patient-ventilator synchrony, especially in presence of air leaks or high ventilatory requirements. Since removing carbon dioxide by means of an artificial lung reduces the minute ventilation required to maintain an acceptable arterial partial pressure of carbon dioxide (PaCO2), the investigators hypothesize that applying Extra-Corporeal CO2 Removal (ECCO2R) in high-risk AECOPD patients may reduce the incidence of NIV failure and improve patient-ventilator interaction. After the beginning of ECCO2R, NIV could be gradually replaced by High Flow Nasal Cannula Oxygen Therapy (HFNCOT), potentially reducing the risk of ventilator induced lung injury, improving patient's comfort and probably allowing the adoption of a more physiologically "noisy" pattern of spontaneous breathing.

Condition or disease Intervention/treatment Phase
Respiratory Failure With Hypercapnia Procedure: HFNCOT+ECCO2R Not Applicable

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease With Extracorporeal Carbon Dioxide Removal Associated With High Flow Nasal Cannula Oxygen Therapy. Pilot Study.
Estimated Study Start Date : July 1, 2019
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : June 2022
Arms and Interventions
Arm Intervention/treatment
Experimental: HFNCOT+ECCO2R
Patients on NIV+ECCO2R who have reached at least for 4 consecutive hours, a RR <25 bpm + pH >7.35 + absence of clinical signs of respiratory distress after treatment with NIV+ECCO2R
 Procedure: HFNCOT+ECCO2R
NIV will be discontinued, the ECCO2R setting will be unchanged (both sweep gas flow and blood flow through the artificial lung) and HFNCOT will be started, titrating the fraction of inspired Oxygen (FiO2) to obtain an oxygen saturation at periphery (SpO2) 88-92%; HFNCOT start temperature will be 31°C, the initial flow rate will be 60 L/min.
Outcome Measures
Primary Outcome Measures :
  1. Number of partecipants failing HFNCOT+ECCO2R treatment with need of restoring NIV or need of invasive mechanical ventilation [ Time Frame: Through study completion, an average of 2 years ]

    ECCO2R+HFNCOT failure criteria are defined by at least two of the following after at least 1 hour of treatment

    1. Respiratory acidosis (pH <7.35)
    2. RR ≥ 30 bpm
    3. Development of progressive hypoxemia (PaO2/FiO2 < 150)
    4. Paradoxical breathing


Secondary Outcome Measures :
  1. Number of partecipants failing NIV+ECCO2R treatment with need of invasive mechanical ventilation [ Time Frame: Through study completion, an average of 2 years ]

    NIV+ECCO2R failure is defined by two of the following occurring for at least 2 hours:

    1. No improvement or worsening of respiratory acidosis (pH <7.35)
    2. RR ≥30 bpm
    3. Development of progressive hypoxemia (PaO2/FiO2 ≤150)

  2. Number of patients treated with ECCO2R reporting one or more side effects due to ECCO2R [ Time Frame: Through study completion, an average of 2 years ]
    1. Bleeding (any bleeding event requiring the administration of 1 U of packed red cells)
    2. Vein perforation at cannula insertion
    3. Hemodynamic instability (80-90 mmHg increase or 30-40 mmHg decrease systolic arterial pressure compared to baseline value or need of vasopressors to maintain systolic blood pressure higher than 85 mmHg or electrocardiogram evidence of ischemia/arrhythmias)
    4. Pneumothorax
    5. Ischemic bowel
    6. Acute kidney failure
    7. Neurological complications (occurrence, after initiation of ECCO2R, of ischemic/hemorrhagic ictus or clinical seizure or cerebral oedema)
    8. Metabolic complications (occurrence, after initiation of ECCO2R of hyperbilirubinemia or glucose≥240 mg/dL)
    9. Thromboembolic complications (occurrence, after initiation of ECCO2R, of deep venous thrombosis, pulmonary embolism)

  3. Variation of pulmonary arterial pressure before and after ECCO2R treatment either in association with NIV or HNFCOT [ Time Frame: Through study completion, an average of 2 years ]
    Echocardiographic measurement

  4. Variation of tricuspid annluar plane systolic excursion before and after ECCO2R treatment either in association with NIV or HNFCOT [ Time Frame: Through study completion, an average of 2 years ]
    Echocardiographic measurement

  5. Variation of respiratory mechanic during ECCO2R+NIV [ Time Frame: Through study completion, an average of 2 years ]
    Measurement of Respiratory Rate (breaths per minute)

  6. Variation of dyspnea during ECCO2R+NIV [ Time Frame: Through study completion, an average of 2 years ]
    Measurement of dyspnea through Borg dyspnea scale. (ranging from a minimum of 0 point, indicating no shortness of breath, to a maximum of 10 points, indicating maximum shortness of breath)

  7. Variation of comfort during ECCO2R+NIV [ Time Frame: Through study completion, an average of 2 years ]
    Measurement of comfort through Visual Analogic Scale for comfort, ranging from a minimum of 0 point, indicating no comfort, to a maximun of 10 point, indicating maximum comfort

  8. Variation of respiratory mechanic during ECCO2R+HFNCOT [ Time Frame: Through study completion, an average of 2 years ]
    Measurement of Respiratory Rate (breaths per minute)

  9. Variation of dyspnea during ECCO2R+HFNCOT [ Time Frame: Through study completion, an average of 2 years ]
    Measurement of dyspnea through Borg dyspnea scale, ranging from a minimum of 0 point, indicating no shortness of breath, to a maximum of 10 points, indicating maximum shortness of breath

  10. Variation of comfort during ECCO2R+HFNCOT [ Time Frame: Through study completion, an average of 2 years ]
    Measurement of comfort through Visual Analogic Scale for comfort, ranging from a minimum of 0 point, indicating no comfort, to a maximun of 10 point, indicating maximum comfort

  11. Variation of breathing pattern during ECCO2R+NIV [ Time Frame: Through study completion, an average of 2 years ]
    Measurement of expiratory tidal volume, expressed in mL

  12. Variation of breathing pattern during ECCO2R+NIV [ Time Frame: Through study completion, an average of 2 years ]
    Measurement of minute ventilation, expressed in liters/minute

  13. Variation of acid-base balance during ECCO2R+NIV [ Time Frame: Through study completion, an average of 2 years ]
    emogasanalysis

  14. Variation of acid-base balance during ECCO2R+HFNCOT [ Time Frame: Through study completion, an average of 2 years ]
    emogasanalysis


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients admitted to Emergency or Pulmonology Department, with history of COPD (pulmonary function test available, any Global Obstructive Lung Disease -GOLD- stage), treated with NIV for acute hypercapnic respiratory failure due to AECOPD defined by:

  • pH <7.35 + PaCO2 >45 mmHg (acute hypercapnic respiratory failure) or pH <7.35 + PaCO2 > 20% of baseline value (acute on chronic hypercapnic respiratory failure)
  • Acute worsening of respiratory symptoms that results in additional therapy
  • Respiratory failure not fully explainable with cardiac failure and at high risk for NIV failure, defined by:
  • No improvement or worsening of respiratory acidosis (pH <7.35 and PaCO2 >45 mmHg) after 2 hours of NIV + one of the following: RR ≥30 bpm; use of accessory respiratory muscle or paradoxical breathing (Combination criteria for NIV failure) or
  • Glasgow Coma Scale ≤ 11 after 2 hours of NIV (Single criteria for NIV failure) or
  • Inability to fit mask (facial deformity/intervention/burns) or marked intolerance to interface because of patient's agitation (Single Criteria for NIV failure)

Exclusion Criteria:

  • Age >80 years old
  • Contraindications to anticoagulation (any of the following: platelet count <30.000/mm3; activated partial thromboplastin time (aPTT) >1,5; stroke or severe head trauma or intracranial arteriovenous malformation or cerebral aneurysm in the previous 3 months; central nervous system mass lesion; history of congenital bleeding diatheses; gastro-intestinal bleeding in the previous 6 weeks; gastro-esophageal varices)
  • Cirrhosis
  • PaO2/FiO2 ≤ 150 mmHg
  • Hemodynamic instability (80-90 mmHg increase or 30-40 mmHg decrease systolic arterial pressure compared to baseline value or need of vasopressors to maintain systolic blood pressure higher than 85 mmHg or electrocardiogram evidence of ischemia/arrhythmias)
  • Body Mass Index ≥37
  • Impending respiratory arrest
  • Catheter access to femoral vein or jugular vein impossible
  • Patient moribund, decision to limit therapeutic interventions
  • Opposition to participate obtained from the patient or their legally acceptable representative
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Giacomo Grasselli, Professor + 39 02 55036708 giacomo.grasselli@unimi.it

Locations
Layout table for location information
Italy
Ospedale Maggiore Policlinico Recruiting
Milan, Italy, 20122
Contact: Giacomo Grasselli, Prof    0255033258    giacomo.grasselli@unimi.it   
Sponsors and Collaborators
Policlinico Hospital
Niguarda Hospital
San Gerardo Hospital
Ospedale San Paolo
Investigators
Layout table for investigator information
Principal Investigator: Giacomo Grasselli, Professor Policlinico Hospital
Tracking Information
First Submitted Date  ICMJE May 27, 2019
First Posted Date  ICMJE June 18, 2019
Last Update Posted Date June 18, 2019
Estimated Study Start Date  ICMJE July 1, 2019
Estimated Primary Completion Date March 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 15, 2019) 		Number of partecipants failing HFNCOT+ECCO2R treatment with need of restoring NIV or need of invasive mechanical ventilation [ Time Frame: Through study completion, an average of 2 years ]
ECCO2R+HFNCOT failure criteria are defined by at least two of the following after at least 1 hour of treatment
  1. Respiratory acidosis (pH <7.35)
  2. RR ≥ 30 bpm
  3. Development of progressive hypoxemia (PaO2/FiO2 < 150)
  4. Paradoxical breathing
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: June 15, 2019)
  • Number of partecipants failing NIV+ECCO2R treatment with need of invasive mechanical ventilation [ Time Frame: Through study completion, an average of 2 years ]
    NIV+ECCO2R failure is defined by two of the following occurring for at least 2 hours:
    1. No improvement or worsening of respiratory acidosis (pH <7.35)
    2. RR ≥30 bpm
    3. Development of progressive hypoxemia (PaO2/FiO2 ≤150)
  • Number of patients treated with ECCO2R reporting one or more side effects due to ECCO2R [ Time Frame: Through study completion, an average of 2 years ]
    1. Bleeding (any bleeding event requiring the administration of 1 U of packed red cells)
    2. Vein perforation at cannula insertion
    3. Hemodynamic instability (80-90 mmHg increase or 30-40 mmHg decrease systolic arterial pressure compared to baseline value or need of vasopressors to maintain systolic blood pressure higher than 85 mmHg or electrocardiogram evidence of ischemia/arrhythmias)
    4. Pneumothorax
    5. Ischemic bowel
    6. Acute kidney failure
    7. Neurological complications (occurrence, after initiation of ECCO2R, of ischemic/hemorrhagic ictus or clinical seizure or cerebral oedema)
    8. Metabolic complications (occurrence, after initiation of ECCO2R of hyperbilirubinemia or glucose≥240 mg/dL)
    9. Thromboembolic complications (occurrence, after initiation of ECCO2R, of deep venous thrombosis, pulmonary embolism)
  • Variation of pulmonary arterial pressure before and after ECCO2R treatment either in association with NIV or HNFCOT [ Time Frame: Through study completion, an average of 2 years ]
    Echocardiographic measurement
  • Variation of tricuspid annluar plane systolic excursion before and after ECCO2R treatment either in association with NIV or HNFCOT [ Time Frame: Through study completion, an average of 2 years ]
    Echocardiographic measurement
  • Variation of respiratory mechanic during ECCO2R+NIV [ Time Frame: Through study completion, an average of 2 years ]
    Measurement of Respiratory Rate (breaths per minute)
  • Variation of dyspnea during ECCO2R+NIV [ Time Frame: Through study completion, an average of 2 years ]
    Measurement of dyspnea through Borg dyspnea scale. (ranging from a minimum of 0 point, indicating no shortness of breath, to a maximum of 10 points, indicating maximum shortness of breath)
  • Variation of comfort during ECCO2R+NIV [ Time Frame: Through study completion, an average of 2 years ]
    Measurement of comfort through Visual Analogic Scale for comfort, ranging from a minimum of 0 point, indicating no comfort, to a maximun of 10 point, indicating maximum comfort
  • Variation of respiratory mechanic during ECCO2R+HFNCOT [ Time Frame: Through study completion, an average of 2 years ]
    Measurement of Respiratory Rate (breaths per minute)
  • Variation of dyspnea during ECCO2R+HFNCOT [ Time Frame: Through study completion, an average of 2 years ]
    Measurement of dyspnea through Borg dyspnea scale, ranging from a minimum of 0 point, indicating no shortness of breath, to a maximum of 10 points, indicating maximum shortness of breath
  • Variation of comfort during ECCO2R+HFNCOT [ Time Frame: Through study completion, an average of 2 years ]
    Measurement of comfort through Visual Analogic Scale for comfort, ranging from a minimum of 0 point, indicating no comfort, to a maximun of 10 point, indicating maximum comfort
  • Variation of breathing pattern during ECCO2R+NIV [ Time Frame: Through study completion, an average of 2 years ]
    Measurement of expiratory tidal volume, expressed in mL
  • Variation of breathing pattern during ECCO2R+NIV [ Time Frame: Through study completion, an average of 2 years ]
    Measurement of minute ventilation, expressed in liters/minute
  • Variation of acid-base balance during ECCO2R+NIV [ Time Frame: Through study completion, an average of 2 years ]
    emogasanalysis
  • Variation of acid-base balance during ECCO2R+HFNCOT [ Time Frame: Through study completion, an average of 2 years ]
    emogasanalysis
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Extra-Corporeal Carbon Dioxide Removal in Exacerbations of Chronic Obstructive Pulmonary Disease
Official Title  ICMJE Treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease With Extracorporeal Carbon Dioxide Removal Associated With High Flow Nasal Cannula Oxygen Therapy. Pilot Study.
Brief Summary Around 20% of the patients requiring hospitalization for Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD) develop hypercapnia, which is associated with an increased risk of death. Once Non Invasive Ventilation (NIV) has been initiated, a reduction in Respiratory Rate (RR) and improvement in pH within 4 h predicts NIV success. If pH <7.25 and RR >35 breath per minutes persist, NIV failure is likely. Worsening acidosis, after initial improvement with NIV, is also associated with a worse prognosis. In addition, it has been shown that delaying intubation in patients at high risk for NIV failure has a negative impact on patient survival. Hence, assessing the risk of NIV failure is extremely important. NIV has some limitations: a) intolerance, discomfort and claustrophobia requiring frequent interruptions; b) poor patient-ventilator synchrony, especially in presence of air leaks or high ventilatory requirements. Since removing carbon dioxide by means of an artificial lung reduces the minute ventilation required to maintain an acceptable arterial partial pressure of carbon dioxide (PaCO2), the investigators hypothesize that applying Extra-Corporeal CO2 Removal (ECCO2R) in high-risk AECOPD patients may reduce the incidence of NIV failure and improve patient-ventilator interaction. After the beginning of ECCO2R, NIV could be gradually replaced by High Flow Nasal Cannula Oxygen Therapy (HFNCOT), potentially reducing the risk of ventilator induced lung injury, improving patient's comfort and probably allowing the adoption of a more physiologically "noisy" pattern of spontaneous breathing.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Respiratory Failure With Hypercapnia
Intervention  ICMJE Procedure: HFNCOT+ECCO2R
NIV will be discontinued, the ECCO2R setting will be unchanged (both sweep gas flow and blood flow through the artificial lung) and HFNCOT will be started, titrating the fraction of inspired Oxygen (FiO2) to obtain an oxygen saturation at periphery (SpO2) 88-92%; HFNCOT start temperature will be 31°C, the initial flow rate will be 60 L/min.
Study Arms  ICMJE Experimental: HFNCOT+ECCO2R
Patients on NIV+ECCO2R who have reached at least for 4 consecutive hours, a RR <25 bpm + pH >7.35 + absence of clinical signs of respiratory distress after treatment with NIV+ECCO2R
Intervention: Procedure: HFNCOT+ECCO2R
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 15, 2019) 		40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2022
Estimated Primary Completion Date March 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Patients admitted to Emergency or Pulmonology Department, with history of COPD (pulmonary function test available, any Global Obstructive Lung Disease -GOLD- stage), treated with NIV for acute hypercapnic respiratory failure due to AECOPD defined by:

  • pH <7.35 + PaCO2 >45 mmHg (acute hypercapnic respiratory failure) or pH <7.35 + PaCO2 > 20% of baseline value (acute on chronic hypercapnic respiratory failure)
  • Acute worsening of respiratory symptoms that results in additional therapy
  • Respiratory failure not fully explainable with cardiac failure and at high risk for NIV failure, defined by:
  • No improvement or worsening of respiratory acidosis (pH <7.35 and PaCO2 >45 mmHg) after 2 hours of NIV + one of the following: RR ≥30 bpm; use of accessory respiratory muscle or paradoxical breathing (Combination criteria for NIV failure) or
  • Glasgow Coma Scale ≤ 11 after 2 hours of NIV (Single criteria for NIV failure) or
  • Inability to fit mask (facial deformity/intervention/burns) or marked intolerance to interface because of patient's agitation (Single Criteria for NIV failure)

Exclusion Criteria:

  • Age >80 years old
  • Contraindications to anticoagulation (any of the following: platelet count <30.000/mm3; activated partial thromboplastin time (aPTT) >1,5; stroke or severe head trauma or intracranial arteriovenous malformation or cerebral aneurysm in the previous 3 months; central nervous system mass lesion; history of congenital bleeding diatheses; gastro-intestinal bleeding in the previous 6 weeks; gastro-esophageal varices)
  • Cirrhosis
  • PaO2/FiO2 ≤ 150 mmHg
  • Hemodynamic instability (80-90 mmHg increase or 30-40 mmHg decrease systolic arterial pressure compared to baseline value or need of vasopressors to maintain systolic blood pressure higher than 85 mmHg or electrocardiogram evidence of ischemia/arrhythmias)
  • Body Mass Index ≥37
  • Impending respiratory arrest
  • Catheter access to femoral vein or jugular vein impossible
  • Patient moribund, decision to limit therapeutic interventions
  • Opposition to participate obtained from the patient or their legally acceptable representative
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Giacomo Grasselli, Professor + 39 02 55036708 giacomo.grasselli@unimi.it
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03990155
Other Study ID Numbers  ICMJE Fondazione IRCCS Ca' Granda
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Giacomo Grasselli, Policlinico Hospital
Study Sponsor  ICMJE Policlinico Hospital
Collaborators  ICMJE
  • Niguarda Hospital
  • San Gerardo Hospital
  • Ospedale San Paolo
Investigators  ICMJE
Principal Investigator: Giacomo Grasselli, Professor Policlinico Hospital
PRS Account Policlinico Hospital
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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